Corneal and ocular surface diseases affects more than 11 million people in US each year. Protein drugs could become effective treatment for corneal and ocular surface diseases. Effective delivery of protein drugs to the ocular surface has been a difficult task that hinders the use of growth factors or cytokines as therapeutic agents for the treatment of ocular surface diseases. Our preliminary study has shown that a living tissue could serve as an in situ "bioreactor" for long-term sustained delivery of proteins at the ocular surface. We hypothesize that sustained protein drug delivery can correct or alleviate ocular surface diseases. Indeed, our preliminary findings in a rabbit corneal epithelial wound-healing model support this hypothesis. In this study, we propose three lines of research to further develop and validate the utility of this technique in two well-studied animal models, and eventually develop products for clinical application. Aim 1: To establish a prototypic product with living cells for ocular surface protein delivery. We will evaluate several candidate cell types for suitability to construct an effective product. Aim 2: To validate an indirect delivery method in rabbit corneal epithelial wound healing model. Our preliminary study has shown that PDGF-beta delivered by early-stage prototypic product accelerates corneal epithelial wound healing in a rabbit model. We will continue this study to evaluate the effects of transplantation techniques on corneal wound healing, and to evaluate whether an optimal dosage of PDGF-beta can be achieved by indirect delivery method. Aim 3: To verify the efficacy of a direct delivery method in rabbit alkali burn induced corneal inflammation model. The direct delivery method will likely provide a higher dosage of therapeutic proteins to the disease site. We will evaluate the effect of anti-inflammatory proteins on controlling corneal inflammation and reducing corneal tissue damages. This will be a three-year tissue-engineering project to develop products that will be used for the treatment of corneal and ocular surface diseases. By the end of the Phase I, we hope to complete Aim 1 study and to have a stable product platform ready for preclinical experiment, and to initiate animal studies proposed in Aim 2 and Aim 3. We intend to complete Aim 2 and Aim 3 studies during the Phase II, including further refinement of the product and completion of rabbit model studies. We intend to move our final developed product into human clinical trial within five years. A successful outcome of this proposed study will likely open up new approaches to better understand the roles of growth factors and cytokines in ocular surface disease processes, and will help us to devise new protein drug based therapy for the treatment of ocular surface diseases. This application proposes a novel mechanism for delivery of protein drugs to the ocular surface. Although the investigators minimize potential hurdles in the project, enthusiasm for this project is relatively high due to the possible benefit for treatment of ocular surface disease.